The purpose of this study was to determine whether high-intensity focused ultrasound (HIFU) is an effective treatment for pancreatic cancer in an athymic nude mouse model. Female athymic nude mice (n=44) were inoculated subcutaneously with 5–7×106 SW1990 human pancreatic cancer cells. Thirty-six animals developed tumours and were randomly divided into three groups: HIFU (n=18), sham treatment (n=9) and control (n=9). The sonographic appearance of the tumours during therapy was recorded. After therapy, the tumours were examined transcutaneously by ultrasound every 4 days for 4 weeks. Tissue samples were taken from the treatment sites and histopathologically examined by light or electron microscopy. Two weeks after HIFU treatment, a 100% reduction in tumour volume was observed in all animals in the HIFU group, whereas tumours in the sham-treated and control groups continued to grow. Pathological examination of HIFU-treated tumour tissue samples showed complete coagulation necrosis in the tumour. Our results indicate that HIFU appears to be an effective therapy for pancreatic tumours in an athymic nude mouse model. Thus, the treatment may hold promise for the clinical treatment of late-stage and recurrent pancreatic cancer.